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RESEARCH PRODUCT
Impact of NADPH oxidase functional polymorphisms in acute myeloid leukemia induction chemotherapy.
David Martínez-cuadrónJosé CerveraPau MontesinosJuan Eduardo Megías-vericatVirginia BosóFederico MoscardóMiguel A. SanzMaría José HerreroMaría José HerreroRebeca Rodríguez-veigaSalvador F. AliñoSalvador F. AliñoLuis RojasLuis RojasJosé Luis PovedaLuis SendraLuis Sendrasubject
0301 basic medicineMaleAnthracyclinePharmacologyBiologyPolymorphism Single NucleotideNephrotoxicity03 medical and health sciences0302 clinical medicineAntineoplastic Combined Chemotherapy ProtocolsGeneticsHumansAgedRetrospective StudiesPharmacologychemistry.chemical_classificationReactive oxygen speciesCardiotoxicityNADPH oxidaseRemission InductionMyeloid leukemiaNADPH OxidasesInduction ChemotherapyMiddle Agedrac GTP-Binding ProteinsRac GTP-Binding ProteinsLeukemia Myeloid Acute030104 developmental biologychemistry030220 oncology & carcinogenesisToxicitybiology.proteinMolecular MedicineFemaleReactive Oxygen Speciesdescription
Efficacy and toxicity of anthracycline treatment in acute myeloid leukemia (AML) is mediated by reactive oxygen species (ROS). NADPH oxidase is the major endogenous source of ROS and a key mediator of oxidative cardiac damage. The impact of NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112, RAC2:rs13058338) was evaluated in 225 adult de novo AML patients. Variant alleles of NCF4 and RAC2 were related to higher complete remission (P=0.035, P=0.016), and CYBA homozygous variant showed lower overall survival with recessive model (P=0.045). Anthracycline-induced cardiotoxicity was associated to NCF4 homozygous variant (P=0.012) and CYBA heterozygous genotype (P=0.027). Novel associations were found between variant allele of CYBA and lower lung and gastrointestinal toxicities, and a protective effect in nephrotoxicity and RAC2 homozygous variant. Moreover, RAC2 homozygous variant was related to delayed thrombocytopenia recovery. This study supports the interest of NADPH oxidase polymorphisms regarding efficacy and toxicity of AML induction therapy, in a coherent integrated manner.
year | journal | country | edition | language |
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2016-08-11 | The pharmacogenomics journal |